A vast majority of conventional biological assays deployed in clinical settings rely on the use of labels. Most commonly, these labels are fluorophores. The use of such labels adds to the complexity and limitations of conventional assays in a number of ways. First, detection of the fluorophore requires an optical excitation source that would, at best, be inefficient if made in silicon. Second, the labeling process itself disadvantageously introduces one or more processing steps. Third, the emission spectra of fluorophores, even quantum dots, are so wide that only a limited number can be delineated with certainty in any one test. While methods employing labels do offer excellent sensitivity in applications ranging from confocal microscopy to immunoassays, they do not lend themselves to high-density, on-chip sensing.
The solution to this—one that has been explored with particular vigor over the past decade—is the use of label-free detection. A number of specific approaches are possible, but the general idea of label-free detection is to use a property inherent to the bio-molecule to detect it directly after it has been specifically captured on or near a sensor without the use of additional labels. A target can posses many detectable properties, but most commonly, label-free sensing mainly utilizes two properties—mass and charge. In both cases, the target could specifically be detected at a sensor site through an interaction, such as that between an antigen and antibody or complementary single stranded nucleic acid sequences, or it can be detected non-specifically.
There are several variations of mass-based sensors, but conventionally the mass of the captured target molecule results in the deflection of a cantilever, the alteration of a propagating acoustic wave, or a change in oscillator resonance properties. Charge-based sensors conventionally fall into devices that are field-effect based, where the charge of a captured target modulates the current through the channel of a semiconductor.